Stem Cell Aging Is Controlled Both Intrinsically and Extrinsically in the Drosophila Ovary
Open accessAbstract
It is widely postulated that tissue aging could be, at least partially, caused by reduction of stem cell number, activity, or both. However, the mechanisms of controlling stem cell aging remain largely a mystery. Here, we use Drosophila ovarian germline stem cells (GSCs) as a model to demonstrate that age-dependent decline in the functions of stem cells and their niche contributes to overall stem cell aging. BMP signaling activity from the niche significantly decreases with age, and increasing BMP signaling can prolong GSC life span and promote their proliferation. In addition, the age-dependent E-cadherin decline in the stem cell-niche junction also contributes to stem cell aging. Finally, overexpression of SOD, an enzyme that helps eliminate free oxygen species, in either GSCs or their niche alone can prolong GSC life span and increase GSC proliferation. Therefore, this study demonstrates that stem cell aging is controlled extrinsically and intrinsically in the Drosophila ovary.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Drosophila cap cells and hub cells become fewer as the flies age.
“In Drosophila, the number of cap cells and hub cells, which serve as support cells for germline stem cells (GSCs) in the testes and ovaries, respectively, decreases with age.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [153]
When the niche is lost, BMP signaling needed to maintain GSCs is impaired.
“This loss of the stem cell niche impairs bone morphogenetic protein (BMP) signaling from the niche that is necessary for GSC maintenance122,153.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [153]
Boosting these signaling molecules reverses the age-related drop in GSC numbers.
“Reduced levels of E-cadherin and Unpaired also contribute to aging of GSC niche by weakening the association between GSCs and cap or hub cells; overexpression of these signaling molecules rescues the age-dependent decline in GSC frequency122,153.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [153]
Lower E-cadherin and Unpaired levels help age the GSC niche by loosening GSC attachment to cap or hub cells.
“Reduced levels of E-cadherin and Unpaired also contribute to aging of GSC niche by weakening the association between GSCs and cap or hub cells; overexpression of these signaling molecules rescues the age-dependent decline in GSC frequency122,153.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [153]
Cites
Notch-Mediated Restoration of Regenerative Potential to Aged Muscle
Conboy, I. M., Conboy, M. J., Smythe, G. M., & Rando, T. A. (2003) · Science · doi:10.1126/science.1087573 · Cited by 1,121 · see citing works
p16INK4a induces an age-dependent decline in islet regenerative potential
Krishnamurthy, J., Ramsey, M. R., Ligon, K. L., Torrice, C., Koh, A., Bonner-Weir, S., & Sharpless, N. E. (2006) · Nature · doi:10.1038/nature05092 · Cited by 1,003 · cited 1× · see citing works
“In the central nervous system, the hematopoietic system, and the pancreas, aging leads to upregulation of p16, a gene responsible for cell senescence, while the deletion of this gene increases the proliferation capacity and prolongs the life span of stem cells (Krishnamurthy et al., 2006; Molofsky et al., 2006).”
BackgroundIncreasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing
Molofsky, A. V., Slutsky, S. G., Joseph, N. M., He, S., Pardal, R., Krishnamurthy, J., Sharpless, N. E., & Morrison, S. J. (2006) · Nature · doi:10.1038/nature05091 · Cited by 972 · cited 1× · see citing works
“In the central nervous system, the hematopoietic system, and the pancreas, aging leads to upregulation of p16, a gene responsible for cell senescence, while the deletion of this gene increases the proliferation capacity and prolongs the life span of stem cells (Krishnamurthy et al., 2006; Molofsky et al., 2006).”
BackgroundEffects of Aging and Niche Microenvironment on Spermatogonial Stem Cell Self-Renewal
Ryu, B.-Y., Orwig, K. E., Oatley, J. M., Avarbock, M. R., & Brinster, R. L. (2006) · Stem Cells · doi:10.1634/stemcells.2005-0580 · Cited by 265 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The aged niche disrupts muscle stem cell quiescence
Chakkalakal, J. V., Jones, K. M., Basson, M. A., & Brack, A. S. (2012) · Nature · doi:10.1038/nature11438 · Cited by 851 · see citing works
Stem cell aging: mechanisms, regulators and therapeutic opportunities
Oh, J., Lee, Y. D., & Wagers, A. J. (2014) · Nature Medicine · doi:10.1038/nm.3651 · Cited by 796 · see citing works
JNK Activity in Somatic Stem Cells Causes Loss of Tissue Homeostasis in the Aging Drosophila Gut
Biteau, B., Hochmuth, C. E., & Jasper, H. (2008) · Cell Stem Cell · doi:10.1016/j.stem.2008.07.024 · Cited by 583 · see citing works
Mechanisms that Regulate Stem Cell Aging and Life Span
Signer, R. A. J., & Morrison, S. J. (2013) · Cell Stem Cell · doi:10.1016/j.stem.2013.01.001 · Cited by 320 · see citing works
piRNA-mediated transgenerational inheritance of an acquired trait
Grentzinger, T., Armenise, C., Brun, C., Mugat, B., Serrano, V., Pelisson, A., & Chambeyron, S. (2012) · Genome Research · doi:10.1101/gr.136614.111 · Cited by 162 · see citing works
Pleiotropic age-dependent effects of mitochondrial dysfunction on epidermal stem cells
Velarde, M. C., Demaria, M., Melov, S., & Campisi, J. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1505675112 · Cited by 77 · see citing works
- Authors
- Pan, L., Chen, S., Weng, C., Call, G., Zhu, D., Tang, H., Zhang, N., & Xie, T.
- Affiliations
- Stowers Institute for Medical Research (US)
- Chinese Academy of Sciences (CN)
- Corresponding author
- Xie, Ting
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2007-10
- Volume
- 1
- Issue
- 4
- Pages
- 458-469
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W1973508705
- Cited by
- 211
- References
- 4
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 8 · 2023: 6 · 2022: 7 · 2021: 3 · 2020: 8 · 2019: 13 · 2018: 9 · 2017: 7 · 2016: 9 · 2015: 14 · 2014: 14 · 2013: 15 · 2012: 29
- FWCI
- 4.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- Funders
- National Institute of General Medical Sciences (2R01 GM64428, R01GM064428)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- stem cell aging, germline stem cells, Drosophila ovary, stem cell niche, BMP signaling, E-cadherin, superoxide dismutase, oxidative stress, stem cell proliferation, extrinsic aging, intrinsic aging
- MeSH terms
- Animals, Cell Count, Drosophila melanogaster, Female, Models, Biological, Ovary, Ovum, Stem Cells, Superoxide Dismutase, Time Factors, Signal Transduction, Cadherins, Cellular Senescence, Bone Morphogenetic Proteins, Cell Proliferation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
